Proteinuria is an abnormal concentration of protein in the urine and it may result from various causes, depending on the specific circumstances.
The kidneys continuously filter the blood to excrete waste products in the urine while retaining useful components such as proteins. However, some conditions can lead to a disruption in this process and cause more protein to be present in the urine than usual.
Normal Protein Filtration
In a healthy person, the filtration of protein from the urine begins in the glomerulus. This capillary network allows the fluid and small solutes to pass into the kidneys but blocks the passage of large molecules such as proteins.
Some proteins with a lower molecular weight may pass this wall but most, including albumin, remain in the bloodstream. The majority of those that do pass into the kidney are reabsorbed in the proximal tubule, and only a small concentration of proteins is usually excreted in the urine.
Transient Causes
Some situations can cause a temporary increase in the concentration of protein in the urine that is not permanent and is not indicative of damage to the function of the kidneys. This may include:
- Extreme temperatures (hot or cold)
- Emotional stress
- Physical exertion
- Fever
Each of these factors has the potential to alter the function of the kidney temporarily and may result in the presence of protein in the urine. However, the urine should return to normal once the cause is removed.
Glomerular
Glomerular disease is the most common cause of severe proteinuria (more than 2 g of protein excreted in the urine within a day.) There are various abnormalities that may have an effect on the permeability of the glomerulus and lead to the excretion of protein in the urine.
Diseases that affect the glomerular filtration and may cause proteinuria can be classified as primary or secondary.
Primary glomerular disease include:
- Minimal change disease
- Idiopathic membranous glomerulonephritis
- Focal segmental glomerulonephritis
- Membranoproliferative glomerulonephritis
- IgA nephropathy
Secondary diseases include:
- Diabetes mellitus
- Lupus nephritis
- Amyloidosis
- Preeclampsia
- Infections
- Chronic renal transplant rejection
- Lymphoma
- Cancer
Additionally, some drugs can affect the function of the glomerulus and may impact the urinary excretion of protein. This includes the use of heroin, non-steroidal anti-inflammatory drugs (NSAIDs), penicillamine or lithium.
Tubular
Decreased reabsorption of proteins in the proximal tubule of those that are able to pass through the glomerulus may cause proteinuria. This is usually associated with moderate cases of proteinuria (less than 2 g of protein excreted in the urine in one day.)
Diseases that may affect the reabsorption of proteins in the proximal tubule include hypertensive nephrosclerosis and tubulointerstitial nephropathy. Additionally, pharmacological treatment with NSAIDs may also affect this and have the potential to contribute to proteinuria.
Additionally, tubulointerstitial disease may arise secondary to an underlying health condition such as:
- Uric acid nephropathy
- Fanconi syndrome
- Sickle cell disease
Overflow
Overflow of proteins into the urine can occur when there is an increased production of proteins with a low molecular weight that are able to pass through the glomerulus. This places an increased load on the proximal tubules to reabsorb the protein and results in an increase in the concentration of proteins that are excreted.
Proteinuria due to overflow is usually associated with conditions such as hemoglobinuria, myoglobinuria, multiple myeloma, amyloidosis or monoclonal gammopathy leukemia.
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Further Reading